Adaptation to chronic continuous hypoxia potentiates Akt/HK2 anti-apoptotic pathway during brief myocardial ischemia/reperfusion insult.

Adaptation to chronic hypoxia represents a potential cardioprotective intervention reducing the extent of acute ischemia/reperfusion (I/R) injury, which is a major cause of death worldwide. The main objective of this study was to investigate the anti-apoptotic Akt/hexokinase 2 (HK2) pathway in hypoxic hearts subjected to I/R insult. Hearts isolated from male Wistar rats exposed either to continuous normobaric hypoxia (CNH; 10% O) or to room air for 3 weeks were perfused according to Langendorff and subjected to 10 min of no-flow ischemia and 10 min of reperfusion.

Altered thyroid status affects myocardial expression of connexin-43 and susceptibility of rat heart to malignant arrhythmias that can be partially normalized by red palm oil intake.

We aimed to study the impact of altered thyroid status on myocardial expression of electrical coupling protein connexin-43 (Cx43), the susceptibility of rats to ventricular fibrillation (VF) and the effects of antioxidant-rich red palm oil (RPO). Adult male and female euthyroid, hyperthyroid (treated with T/T), hypothyroid (treated with methimazole) Wistar rats supplemented or not with RPO for 6 weeks were used. Function of isolated perfused heart and VF threshold were determined.

β-Adrenergic signaling in rat heart is similarly affected by continuous and intermittent normobaric hypoxia.

Chronic hypoxia may produce a cardioprotective phenotype characterized by increased resistance to ischemia-reperfusion injury. Nevertheless, the molecular basis of cardioprotective effects of hypoxia is still not quite clear. The present study investigated the consequences of a 3-week adaptation to cardioprotective (CNH, continuous normobaric hypoxia) and nonprotective (INH, intermittent normobaric hypoxia; 23 h/day hypoxia followed by 1 h/day reoxygenation) regimen of hypoxia on β-adrenergic signaling in the rat myocardium.

Circadian Dexras1 in rats: Development, location and responsiveness to light.

Dexras1 has been shown to exhibit clock-dependent rhythm in mice suprachiasmatic nucleus (SCN), and its genetic deletion modulates circadian responses to photic and nonphotic cues. We show that the rhythmic expression of Dexras1 mRNA and protein in rat SCN already oscillates with low amplitude at postnatal day 3 and can be detected as early as embryonic day 20. In contrast, its expression in peripheral tissues is not rhythmic in adult rats either.

Cardioprotective adaptation of rats to intermittent hypobaric hypoxia is accompanied by the increased association of hexokinase with mitochondria.

Chronic hypoxia increases the myocardial resistance to acute ischemia-reperfusion injury by affecting the mitochondrial redox balance. Hexokinase (HK) bears a high potential to suppress the excessive formation of reactive oxygen species because of its increased association with mitochondria, thereby inhibiting the membrane permeability transition pore opening and preventing cell death. The purpose of this study was to determine the effect of severe intermittent hypobaric hypoxia (7,000 m, 8 h/day, 5 wk) on the function and colocalization of HK isoforms with mitochondria in the left (LV) and right ventricles of rat myocardium.

Cardioprotective and nonprotective regimens of chronic hypoxia diversely affect the myocardial antioxidant systems.

It has been documented that adaptation to hypoxia increases myocardial tolerance to ischemia-reperfusion (I/R) injury depending on the regimen of adaptation. Reactive oxygen species (ROS) formed during hypoxia play an important role in the induction of protective cardiac phenotype. On the other hand, the excess of ROS can contribute to tissue damage caused by I/R.

Association of MTHFR genetic variants C677T and A1298C on predisposition to spontaneous abortion in Slavonic population.

Aim: Up to 20% of pregnancies end in the first trimester by spontaneous abortion but the cause of a large proportion remains unexplained. The aim of this study was to investigate the role of two common variants (rs1801133, C677T and rs1801131, A1298C) within the MTHFR gene in the genetic determination of spontaneous abortions.

Methods: DNA from 464 tissue samples of spontaneous abortions and population sample of adults (N=2,486) were genotyped for both MTHFR polymorphisms of interest.

Chronic hypoxia enhances expression and activity of mitochondrial creatine kinase and hexokinase in the rat ventricular myocardium.

Background: Creatine kinase (CK) and hexokinase (HK) play a key role in myocardial energy homeostasis. We aimed to determine CK and HK expression and enzyme activity in the left (LV) and right (RV) ventricles of rats adapted for 3 weeks to normobaric hypoxia (10 % O2) either continuously (CNH) or intermittently with 1-h or 16-h normoxic episode per day.

Methods: The Real-Time RT-PCR, Western blot, and enzyme-coupled assays were used.

Transgenic rescue of defective Cd36 enhances myocardial adenylyl cyclase signaling in spontaneously hypertensive rats.

Dysfunction or abnormalities in the regulation of fatty acid translocase Cd36, a multifunctional membrane protein participating in uptake of long-chain fatty acids, has been linked to the development of heart diseases both in animals and humans. We have previously shown that the Cd36 transgenic spontaneously hypertensive rat (SHR-Cd36), with a wild type Cd36, has higher susceptibility to ischemic ventricular arrhythmias when compared to spontaneously hypertensive rat (SHR) carrying a mutant Cd36 gene, which may have been related to increased β-adrenergic responsiveness of these animals (Neckar et al., 2012 Physiol.

Right-to-left ventricular differences in the expression of mitochondrial hexokinase and phosphorylation of Akt.

Background/aims: Hexokinase (HK) is a key glycolytic enzyme which promotes the maintenance of glucose homeostasis in cardiomyocytes. HK1 isoform is predominantly bound to the outer mitochondrial membrane and highly supports oxidative phosphorylation by increasing the availability of ADP for complex V of the respiratory chain. HK2 isoform is under physiological conditions predominantly localized in the cytosol and upon stimulation of PI3K/ Akt pathway associates with mitochondria and thus can prevent apoptosis.

Is screening for hereditary thrombophilia indicated in first early pregnancy loss?

Objective: The aim of the study was to evaluate the importance of screening for thrombophilic mutations after the first early pregnancy loss.

Setting: Thrombophilic mutations were examined in a sample of 100 women with at least one miscarriage. DNA was isolated from venous blood sample.

Analysis of the potential role of Apolipoprotein E polymorphism in genetic predisposition to spontaneous abortion.

Problem: Up to 20% of pregnancies end in the first trimester by spontaneous abortion, but a significant number remains unexplained. The aim of this study is to investigate the role of variants within the gene for apolipoprotein E (APOE) in the genetic determination of spontaneous abortions.

Method Of Study: We collected DNA from 410 tissue samples of spontaneous abortions, and APOE was genotyped by PCR-RFLP method.